The lessons learned from p-octiphenyl β-barrel pores are applied to the rational design of synthetic multifunctional pore 1 that is unstable but inert, two characteristics proposed to be ideal for practical applications. Nonlinear dependence on monomer concentration provided direct evidence that pore 1 is tetrameric (n = 4.0), unstable, and “invisible,â€� i.e., incompatible with structural studies by conventional methods. The long lifetime of high-conductance single pores in planar bilayers demonstrated that rigid-rod β-barrel 1 is inert and large (d ≈ 12 Ã…). Multifunctionality of rigid-rod β-barrel 1 was confirmed by adaptable blockage of pore host 1 with representative guests in planar (8-hydroxy-1,3,6-pyrenetrisulfonate, K_D = 190 μM, n = 4.9) and spherical bilayers (poly-l-glutamate, K_D ≤ 105 nM, n = 1.0; adenosine triphosphate, K_D = 240 μM, n = 2.0) and saturation kinetics for the esterolysis of a representative substrate (8-acetoxy-1,3,6-pyrenetrisulfonate, K_M = 0.6 μM). The thermodynamic instability of rigid-rod β-barrel 1 provided unprecedented access to experimental evidence for supramolecular catalysis (n = 3.7). Comparison of the obtained k_cat = 0.03 min^-1 with the k_cat ≈ 0.18 min^-1 for stable analogues gave a global K_D ≈ 39 μM³ for supramolecular catalyst 1 with a monomer/barrel ratio ≈ 20 under experimental conditions. The demonstrated “invisibilityâ€� of supramolecular multifunctionality identified molecular modeling as an attractive method to secure otherwise elusive insights into structure. The first molecular mechanics modeling (MacroModel, MMFF94) of multifunctional rigid-rod β-barrel pore hosts 1 with internal 1,3,6-pyrenetrisulfonate guests is reported.